Genes & development最新文献

英文中文

LINE-1, the NORth star of nucleolar organization

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2025-01-10 DOI: 10.1101/gad.352583.124

Misaki Matsuo, Gael Cristofari

Long interspersed element-1 (LINE-1) retrotransposons are abundant transposable elements in mammals and significantly influence chromosome structure, chromatin organization, and 3D genome architecture. In this issue of Genes & Development, Ataei et al. (doi:10.1101/gad.351979.124) identify a homininae-specific LINE-1 element within nucleolar ogranizer regions (NORs) that is specifically transcribed in naïve human embryonic stem cells. Deletion or silencing of this element disrupts nucleolar organization and function and alters cellular identity. These findings provide novel insights into the role of retrotransposons in genome organization and suggest that individual LINE-1 elements may have evolved specialized roles.

引用次数: 0

ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2025-01-10 DOI: 10.1101/gad.352129.124

Sushant Bangru, Jackie Chen, Nicholas Baker, Diptatanu Das, Ullas V. Chembazhi, Jessica M. Derham, Sandip Chorghade, Waqar Arif, Frances Alencastro, Andrew W. Duncan, Russ P. Carstens, Auinash Kalsotra

Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of epithelial splicing regulatory protein 2 (ESRP2) stimulates processing of liver-specific microRNA (miR-122) to facilitate polyploidization, maturation, and functional competence of hepatocytes. By determining transcriptome-wide protein–RNA interactions in vivo and integrating them with single-cell and bulk hepatocyte RNA-seq data sets, we delineated an ESRP2-driven RNA processing program that drives sequential replacement of fetal-to-adult transcript isoforms. Specifically, ESRP2 binds the primary miR-122 host gene transcript to promote its processing/biogenesis. Combining constitutive and inducible ESRP2 gain- and loss-of-function mouse models with miR-122 rescue experiments, we demonstrated that timed activation of ESRP2 augments the miR-122-driven program of cytokinesis failure, ensuring the proper onset and extent of hepatocyte polyploidization.

{"title":"ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation","authors":"Sushant Bangru, Jackie Chen, Nicholas Baker, Diptatanu Das, Ullas V. Chembazhi, Jessica M. Derham, Sandip Chorghade, Waqar Arif, Frances Alencastro, Andrew W. Duncan, Russ P. Carstens, Auinash Kalsotra","doi":"10.1101/gad.352129.124","DOIUrl":"https://doi.org/10.1101/gad.352129.124","url":null,"abstract":"Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of epithelial splicing regulatory protein 2 (ESRP2) stimulates processing of liver-specific microRNA (miR-122) to facilitate polyploidization, maturation, and functional competence of hepatocytes. By determining transcriptome-wide protein–RNA interactions in vivo and integrating them with single-cell and bulk hepatocyte RNA-seq data sets, we delineated an ESRP2-driven RNA processing program that drives sequential replacement of fetal-to-adult transcript isoforms. Specifically, ESRP2 binds the primary miR-122 host gene transcript to promote its processing/biogenesis. Combining constitutive and inducible ESRP2 gain- and loss-of-function mouse models with miR-122 rescue experiments, we demonstrated that timed activation of ESRP2 augments the miR-122-driven program of cytokinesis failure, ensuring the proper onset and extent of hepatocyte polyploidization.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"319 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges. 通过空间转录组学解读正常和癌症干细胞龛位：机遇与挑战。

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2025-01-07 DOI: 10.1101/gad.351956.124

Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang

Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional plasticity. Investigating these properties across diverse organs during normal development and tumorigenesis is of paramount research interest and translational potential. Advancements in next-generation sequencing (NGS), single-cell transcriptomics, and spatial transcriptomics have ushered in a new era in cancer research, providing high-resolution and comprehensive molecular maps of diseased tissues. Various spatial technologies, with their unique ability to measure the location and molecular profile of a cell within tissue, have enabled studies on intratumoral architecture and cellular cross-talk within the specific niches. Moreover, delineation of spatial patterns for niche-specific properties such as hypoxia, glucose deprivation, and other microenvironmental remodeling are revealed through multilevel spatial sequencing. This tremendous progress in technology has also been paired with the advent of computational tools to mitigate technology-specific bottlenecks. Here we discuss how different spatial technologies are used to identify NSCs and CSCs, as well as their associated niches. Additionally, by exploring related public data sets, we review the current challenges in characterizing such niches, which are often hindered by technological limitations, and the computational solutions used to address them.

癌症干细胞（CSCs）通常表现出类似干细胞的特性，这取决于其生态位内错综复杂的促进干细胞生态系统。CSCs与其生态位之间的相互作用与肿瘤的异质性和抗药性有关。正常干细胞（NSCs）和CSCs具有相同的干性特征和共同的微环境成分，表现出显著的表型和功能可塑性。研究正常发育和肿瘤发生过程中不同器官的这些特性具有重要的研究意义和转化潜力。下一代测序（NGS）、单细胞转录组学和空间转录组学的进步开创了癌症研究的新纪元，为病变组织提供了高分辨率和全面的分子图谱。各种空间技术具有测量组织内细胞位置和分子特征的独特能力，因此可以研究特定龛位内的瘤内结构和细胞交叉对话。此外，通过多层次空间测序技术，还能发现缺氧、葡萄糖剥夺和其他微环境重塑等特定龛位特性的空间模式。在技术取得巨大进步的同时，计算工具的出现也缓解了特定技术的瓶颈。在这里，我们将讨论如何利用不同的空间技术来识别NSCs和CSCs及其相关的龛位。此外，通过对相关公共数据集的探索，我们回顾了目前在描述此类壁龛特征方面所面临的挑战（这些挑战往往受到技术限制的阻碍），以及用于解决这些问题的计算解决方案。

{"title":"Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges.","authors":"Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang","doi":"10.1101/gad.351956.124","DOIUrl":"10.1101/gad.351956.124","url":null,"abstract":"Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional plasticity. Investigating these properties across diverse organs during normal development and tumorigenesis is of paramount research interest and translational potential. Advancements in next-generation sequencing (NGS), single-cell transcriptomics, and spatial transcriptomics have ushered in a new era in cancer research, providing high-resolution and comprehensive molecular maps of diseased tissues. Various spatial technologies, with their unique ability to measure the location and molecular profile of a cell within tissue, have enabled studies on intratumoral architecture and cellular cross-talk within the specific niches. Moreover, delineation of spatial patterns for niche-specific properties such as hypoxia, glucose deprivation, and other microenvironmental remodeling are revealed through multilevel spatial sequencing. This tremendous progress in technology has also been paired with the advent of computational tools to mitigate technology-specific bottlenecks. Here we discuss how different spatial technologies are used to identify NSCs and CSCs, as well as their associated niches. Additionally, by exploring related public data sets, we review the current challenges in characterizing such niches, which are often hindered by technological limitations, and the computational solutions used to address them.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"64-85"},"PeriodicalIF":7.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genes & Development aims for an expansive horizon

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2025-01-01 DOI: 10.1101/gad.352534.124

Andrew Dillin

Dear Colleagues,

引用次数: 0

Genes & Development: an evolution

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2025-01-01 DOI: 10.1101/gad.352552.124

John R. Inglis

With this first Genes & Development issue of 2025, it is my great pleasure to welcome new editorial leadership to the journal.

引用次数: 0

E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2024-12-30 DOI: 10.1101/gad.352010.124

Alexis U. Oguh, Matthew W. Haemmerle, Sabyasachi Sen, Andrea V. Rozo, Shristi Shrestha, Jean-Philippe Cartailler, Hossein Fazelinia, Hua Ding, Sam Preza, Juxiang Yang, Xiaodun Yang, Lori Sussel, Juan R. Alvarez-Dominguez, Nicolai Doliba, Lynn A. Spruce, Rafael Arrojo e Drigo, Doris A. Stoffers

The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific Spop deletion mouse strain (Spop^βKO) and found that Spop is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux. Integration of proteomic, TF-regulatory gene network, and biochemical analyses identified XBP1 as a functionally important SPOP substrate in pancreatic β cells. Furthermore, loss of SPOP strengthened the IRE1α–XBP1 axis of unfolded protein response (UPR) signaling. ER stress promoted proteasomal degradation of SPOP, supporting a model whereby SPOP fine-tunes XBP1 activation during the UPR. These results position SPOP as a regulator of β-cell function and proper UPR activation.

{"title":"E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells","authors":"Alexis U. Oguh, Matthew W. Haemmerle, Sabyasachi Sen, Andrea V. Rozo, Shristi Shrestha, Jean-Philippe Cartailler, Hossein Fazelinia, Hua Ding, Sam Preza, Juxiang Yang, Xiaodun Yang, Lori Sussel, Juan R. Alvarez-Dominguez, Nicolai Doliba, Lynn A. Spruce, Rafael Arrojo e Drigo, Doris A. Stoffers","doi":"10.1101/gad.352010.124","DOIUrl":"https://doi.org/10.1101/gad.352010.124","url":null,"abstract":"The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific Spop deletion mouse strain (SpopβKO) and found that Spop is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux. Integration of proteomic, TF-regulatory gene network, and biochemical analyses identified XBP1 as a functionally important SPOP substrate in pancreatic β cells. Furthermore, loss of SPOP strengthened the IRE1α–XBP1 axis of unfolded protein response (UPR) signaling. ER stress promoted proteasomal degradation of SPOP, supporting a model whereby SPOP fine-tunes XBP1 activation during the UPR. These results position SPOP as a regulator of β-cell function and proper UPR activation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"36 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternative splicing controls pan-neuronal homeobox gene expression

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2024-12-27 DOI: 10.1101/gad.352184.124

Eduardo Leyva-Díaz, Michael Cesar, Karinna Pe, José Ignacio Jordá-Llorens, Jessica Valdivia, Oliver Hobert

The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of Caenorhabditis elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 (“CASP of nematodes”) in C. elegans. How gene expression from this complex locus is controlled—and, in C. elegans, directed to all cells of the nervous system—has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75, the C. elegans homolog of vertebrate CELF proteins. During embryogenesis, the cone-1&ceh-44 locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript exclusively in the nervous system. Hence, UNC-75/CELF-mediated alternative splicing not only directs pan-neuronal gene expression but also excludes a phylogenetically deeply conserved golgin from the nervous system, paralleling surprising spatial specificities of another golgin that we describe here as well. Our findings provide novel insights into how all cells in a nervous system acquire pan-neuronal identity features and reveal unanticipated cellular specificities in Golgi apparatus composition.

{"title":"Alternative splicing controls pan-neuronal homeobox gene expression","authors":"Eduardo Leyva-Díaz, Michael Cesar, Karinna Pe, José Ignacio Jordá-Llorens, Jessica Valdivia, Oliver Hobert","doi":"10.1101/gad.352184.124","DOIUrl":"https://doi.org/10.1101/gad.352184.124","url":null,"abstract":"The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of Caenorhabditis elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 (“CASP of nematodes”) in C. elegans. How gene expression from this complex locus is controlled—and, in C. elegans, directed to all cells of the nervous system—has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75, the C. elegans homolog of vertebrate CELF proteins. During embryogenesis, the cone-1&ceh-44 locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript exclusively in the nervous system. Hence, UNC-75/CELF-mediated alternative splicing not only directs pan-neuronal gene expression but also excludes a phylogenetically deeply conserved golgin from the nervous system, paralleling surprising spatial specificities of another golgin that we describe here as well. Our findings provide novel insights into how all cells in a nervous system acquire pan-neuronal identity features and reveal unanticipated cellular specificities in Golgi apparatus composition.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"15 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NKX2.2 and KLF4 cooperate to regulate α-cell identity

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2024-12-20 DOI: 10.1101/gad.352193.124

Elliott P. Brooks, McKenna R. Casey, Kristen L. Wells, Tsung-Yun Liu, Madeline Van Orman, Lori Sussel

Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.2 is critical for the identity of pancreatic islet α cells by directly activating α-cell genes and repressing alternate islet cell fate genes. When compared with the known role of NKX2.2 in islet β cells, we demonstrate that NKX2.2 regulates α-cell genes, facilitated in part by α-cell-specific DNA binding at gene promoters. Furthermore, we have identified the reprogramming factor KLF4 as having enriched expression in α cells, where it co-occupies NKX2.2-bound α-cell promoters, is necessary for NKX2.2 promoter occupancy in α cells, and coregulates many NKX2.2 α-cell transcriptional targets. Overexpression of Klf4 in β cells is sufficient to manipulate chromatin accessibility, increase binding of NKX2.2 at α-cell-specific promoter sites, and alter expression of NKX2.2-regulated cell-specific targets. This study identifies KLF4 as a novel α-cell factor that cooperates with NKX2.2 to regulate α-cell identity.

{"title":"NKX2.2 and KLF4 cooperate to regulate α-cell identity","authors":"Elliott P. Brooks, McKenna R. Casey, Kristen L. Wells, Tsung-Yun Liu, Madeline Van Orman, Lori Sussel","doi":"10.1101/gad.352193.124","DOIUrl":"https://doi.org/10.1101/gad.352193.124","url":null,"abstract":"Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.2 is critical for the identity of pancreatic islet α cells by directly activating α-cell genes and repressing alternate islet cell fate genes. When compared with the known role of NKX2.2 in islet β cells, we demonstrate that NKX2.2 regulates α-cell genes, facilitated in part by α-cell-specific DNA binding at gene promoters. Furthermore, we have identified the reprogramming factor KLF4 as having enriched expression in α cells, where it co-occupies NKX2.2-bound α-cell promoters, is necessary for NKX2.2 promoter occupancy in α cells, and coregulates many NKX2.2 α-cell transcriptional targets. Overexpression of Klf4 in β cells is sufficient to manipulate chromatin accessibility, increase binding of NKX2.2 at α-cell-specific promoter sites, and alter expression of NKX2.2-regulated cell-specific targets. This study identifies KLF4 as a novel α-cell factor that cooperates with NKX2.2 to regulate α-cell identity.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"93 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2024-12-20 DOI: 10.1101/gad.352120.124

Azad Alizada, Gregory J. Hannon, Benjamin Czech Nicholson

The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using Drosophila as a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells. Ectopic expression of Ovo in ovarian somatic cells activates germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3, and Vasa, leading to assembly of perinuclear cellular structures resembling nuage bodies of germ cells. We found that in ovarian somatic cells, transcription of ovo is repressed by l(3)mbt, thus preventing expression of germline piRNA pathway genes in the soma. Cross-species ChIP-seq and motif analyses demonstrate that Ovo is binding to genomic CCGTTA motifs within the promoters of germline piRNA pathway genes, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. Our results also show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from insects to humans.

{"title":"Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells","authors":"Azad Alizada, Gregory J. Hannon, Benjamin Czech Nicholson","doi":"10.1101/gad.352120.124","DOIUrl":"https://doi.org/10.1101/gad.352120.124","url":null,"abstract":"The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using Drosophila as a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells. Ectopic expression of Ovo in ovarian somatic cells activates germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3, and Vasa, leading to assembly of perinuclear cellular structures resembling nuage bodies of germ cells. We found that in ovarian somatic cells, transcription of ovo is repressed by l(3)mbt, thus preventing expression of germline piRNA pathway genes in the soma. Cross-species ChIP-seq and motif analyses demonstrate that Ovo is binding to genomic CCGTTA motifs within the promoters of germline piRNA pathway genes, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. Our results also show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from insects to humans.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"147 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells

IF 10.5 1区生物学 Q1 CELL BIOLOGY

Genes & development

Pub Date : 2024-12-20 DOI: 10.1101/gad.351979.124

Lamisa Ataei, Juan Zhang, Simon Monis, Krystyna Giemza, Kirti Mittal, Joshua Yang, Mayu Shimomura, Brian McStay, Michael D. Wilson, Miguel Ramalho-Santos

The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes. Distal junctions (DJs) are ∼400 kb sequences adjacent to rDNA arrays that are thought to anchor them at the nucleolus, although the underlying regulatory elements remain unclear. Here we show that DJs display a dynamic chromosome conformation profile in human embryonic stem cells (hESCs). We identified a primate-specific, full-length insertion of the retrotransposon long interspersed nuclear element 1 (LINE1) in a conserved position across all human DJs. This DJ-LINE1 locus interacts with specific regions of the DJ and is upregulated in naïve hESCs. CRISPR-based deletion and interference approaches revealed that DJ-LINE1 contributes to nucleolar positioning of the DJs. Moreover, we found that the expression of DJ-LINE1 is required for maintenance of the structure and transcriptional output of the nucleolus in hESCs. Silencing of DJ-LINE1 leads to loss of self-renewal, disruption of the landscape of chromatin accessibility, and derepression of earlier developmental programs in naïve hESCs. This work uncovers specific LINE1 elements with a fundamental role in nucleolar organization in hESCs and provides new insights into how the nucleolus functions as a key genome-organizing hub.

{"title":"LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells","authors":"Lamisa Ataei, Juan Zhang, Simon Monis, Krystyna Giemza, Kirti Mittal, Joshua Yang, Mayu Shimomura, Brian McStay, Michael D. Wilson, Miguel Ramalho-Santos","doi":"10.1101/gad.351979.124","DOIUrl":"https://doi.org/10.1101/gad.351979.124","url":null,"abstract":"The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes. Distal junctions (DJs) are ∼400 kb sequences adjacent to rDNA arrays that are thought to anchor them at the nucleolus, although the underlying regulatory elements remain unclear. Here we show that DJs display a dynamic chromosome conformation profile in human embryonic stem cells (hESCs). We identified a primate-specific, full-length insertion of the retrotransposon long interspersed nuclear element 1 (LINE1) in a conserved position across all human DJs. This DJ-LINE1 locus interacts with specific regions of the DJ and is upregulated in naïve hESCs. CRISPR-based deletion and interference approaches revealed that DJ-LINE1 contributes to nucleolar positioning of the DJs. Moreover, we found that the expression of DJ-LINE1 is required for maintenance of the structure and transcriptional output of the nucleolus in hESCs. Silencing of DJ-LINE1 leads to loss of self-renewal, disruption of the landscape of chromatin accessibility, and derepression of earlier developmental programs in naïve hESCs. This work uncovers specific LINE1 elements with a fundamental role in nucleolar organization in hESCs and provides new insights into how the nucleolus functions as a key genome-organizing hub.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"13 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Genes & development

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀